The more recent developments in the field of the gadolinium-containing MR contrast agents (EP 0448191 B1, U.S. Pat. No. 5,980,864, EP 0643705 B1, EP 0986548 B1, EP 0596586 B1) include the MRI contrast agent gadobutrol (Gadovist® 1.0) which has been approved for a relatively long time in Europe and more recently also in the USA under the name Gadavist® (Bayer HealthCare LLC, Whippany, N.J.).
The contrast action is based on gadobutrol, a non-ionic complex consisting of gadolinium(III) and the macrocyclic ligand dihydroxyhydroxymethyl propyltetraazacyclododecanetriacetic acid (butrol), which leads inter alia at the clinically recommended dosages to shorter relaxation times of protons of the tissue water.

Owing to their importance as imaging diagnostics, in particular as MRI diagnostics, metal complexes, in particular the gadolinium complex N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane “gadobutrol” (DE 4009119) can be prepared by various routes. In spite of progress made compared to the original processes, there is still a need for syntheses which are more environmentally friendly and cost-effective, and are suitable for implementation especially on an industrial scale. In particular, there is a high demand for high product throughput and high quality. In more recent years, there has been a trend to replace some or all of the open-chain contrast agents by cyclic contrast agents. Here, there is the requirement to produce particularly pure products, which should additionally also be cost-effective. In general, these are requirements which are mutually exclusive, since high-quality products are expensive to produce owing to specific purification measures. For optimum quality control, it is necessary to have available a highly reliable method for analytical determination which allows detection and quantification of all minor components present.
Accordingly, there is a need for an economically favourable process for producing gadobutrol, and also for an analytical method which allows the selective detection and quantification of minimal amounts of minor components (production monitoring).